The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.
Amphetamine ; Animals ; Glycogen Synthase Kinases ; Humans ; Membrane Proteins ; Microinjections ; Negotiating ; Neurons ; Nucleus Accumbens ; Phosphorylation ; Phosphotransferases ; Plastics ; Proto-Oncogene Proteins c-akt ; Rats ; Reward ; Signal Transduction ; Street Drugs ; Substance-Related Disorders

Limonene is a cyclic terpene found in citrus essential oils and inhibits methamphetamine-induced locomotor activity. Drug dependence is a severe neuropsychiatric condition that depends in part on changes in neurotransmission and neuroadaptation, induced by exposure to recreational drugs such as morphine and methamphetamine. In this study, we investigated the effects of limonene on the psychological dependence induced by drug abuse. The development of sensitization, dopamine receptor supersensitivity, and conditioned place preferences in rats was measured following administration of limonene (10 or 20 mg/kg) and methamphetamine (1 mg/kg) for 4 days. Limonene inhibits methamphetamine-induced sensitization to locomotor activity. Expression of dopamine receptor supersensitivity induced by apomorphine, a dopamine receptor agonist, was significantly reduced in limonene-pretreated rats. However, there was no significant difference in methamphetamine-induced conditioned place preferences between the limonene and control groups. These results suggest that limonene may ameliorate drug addiction-related behaviors by regulating postsynaptic dopamine receptor supersensitivity.
Animals ; Apomorphine ; Citrus ; Dopamine Agonists ; Dopamine ; Methamphetamine ; Morphine ; Motor Activity ; Oils, Volatile ; Rats ; Receptors, Dopamine ; Street Drugs ; Substance-Related Disorders ; Synaptic Transmission

OBJECTIVES: To identify the associations of characteristics of the neighborhood environment with substance abuse among clients receiving treatment for drug abuse in Thailand. METHODS: A cross-sectional study was conducted of 1128 drug addicts from 28 neighborhoods who were receiving treatment at all 7 compulsory drug detention centers in Thailand. A trained interviewer conducted structured interviews with the subjects about substance use and the perceived neighborhood environment in their community. A multilevel logistic regression model was applied to estimate the effects of the neighborhood environment on substance use. RESULTS: The majority of participants, 53.8% only used methamphetamine pills, 31.3% used other illicit drugs as well as methamphetamine pills, and 14.9% used an illicit drug other than methamphetamine. Three neighborhood characteristics were associated with substance use. A 1-unit increase in the perceived neighborhood cohesion score was associated with a 15% reduction in methamphetamine pill use and an 11% reduction of the use of both methamphetamine pills and another illicit drug. Conversely, a 1-unit increase in perceived neighborhood crime predicted 19 and 14% increases in the use of methamphetamine pills and the use of both methamphetamine pills and another illicit drug, respectively. In addition, a 1-unit increase in the scores for stigma surrounding addiction corresponded to a 25% increase of the use of methamphetamine pills and a 12% increase in the use of both methamphetamine pills and another illicit drug. CONCLUSIONS: Substance use among drug addicts was influenced by characteristics of the neighborhood environment. Therefore, prevention and intervention strategies should be designed based on a consideration of the impact of neighborhood context on substance use behaviors.
Crime ; Cross-Sectional Studies ; Drug Users ; Humans ; Logistic Models ; Methamphetamine ; Residence Characteristics ; Street Drugs ; Substance-Related Disorders ; Thailand

Psychostimulants are a broad class of sympathomimetic drugs that include drugs of abuse, such as illegal substances, as well as therapeutic drugs, such as methylphenidate and modafinil. The common effect of psychostimulants is to improve motivation, mood, movement, energy, wakefulness, arousal, anorexia and attention. Methylphenidate and modafinil are psychostimulants used in the treatment of attention deficit hyperactivity disorder and narcolepsy. They have also been found to be effective for treating certain cognitive disorders that result in secondary depression or profound apathy, obesity, cancer-related fatigue as well as in specific treatment-resistant depressions as an augmentation therapy with antidepressants. Psychostimulants are also used in an non-medical manner, such as cognitive and/or performance enhancers in healthy population. However, the most limiting adverse effect of psychostimulants is their vulnerability to psychological and physical dependence. Therefore, the abuse and misuse of stimulants, including methylphenidate and modafinil, for the purpose of neuroenhancement is an issue of concern throughout the world including Korea. Although several recent studies have reported on the cognitive and performance enhancement effects of methylphenidate and modafinil in healthy population, psychostimulants should be administered with discretion in the light of their potential adverse effects and the lacks of long-standing efficacy.
Anorexia ; Antidepressive Agents ; Apathy ; Arousal ; Attention Deficit Disorder with Hyperactivity ; Depression ; Fatigue ; Korea ; Methylphenidate ; Motivation ; Narcolepsy ; Obesity ; Street Drugs ; Sympathomimetics ; Wakefulness

BACKGROUND: Illicit drug use is emerging as an important Public Health issue among Filipinos nowadays. This calls for all primary health care facilities to provide services to persons who use drugs.
OBJECTIVES: The study aimed to determine the socio-demographic profile of substance abuse at the municipal level.
METHODS: This study was conducted in the Municipality of Rosario, Agusan del Sur with fifty (50) study participants who were identified as low to moderate risk drug users. Data gathering procedure utilized the Key Informant Interview with a structured survey questionnaire.
RESULTS: Results of the study showed that the majority of the drug abusers were male adults between 20-30 years of age with low educational attainment and engagement in risky and hard labored occupations. Methamphetamine was the most commonly-abused drug with curiosity and stamina at work as the major causes of drug abuse. Analysis of Variance as to extent of drug use between and among age groups indicates significant difference which strongly suggests that interventions should be responsive to the needs of the different age groups.
CONCLUSION: Drug-free community is not far if concerned efforts from all sectors of society be done to help the users become partners for social change.

Human ; Male ; Adult ; Methamphetamine ; Drug Users ; Substance-related Disorders ; Risk ; Occupations ; Street Drugs ; Analysis Of Variance ; Primary Health Care

The demand for rapid and broad clinical toxicology screens is on the rise. Recently, a new rapid toxicology screening test, the Triage TOX Drug Screen (Alere Inc., USA), which can simultaneously detect 11 drugs of abuse and therapeutic drugs with an instrument-read cartridge, was developed. In the present study, we evaluated the efficacy of this new on-site immunoassay using 105 urine specimens; the results were compared with those obtained by using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-TMS). Precision was evaluated according to the CLSI EP12-A2 for analyte concentrations near the cutoff, including C₅₀ and±30% of C₅₀, for each drug using standard materials. The C₅₀ specimens yielded 35–65% positive results and the ±30% concentration range of all evaluated drugs encompassed the C₅–C₉₅ interval. The overall percent agreement of the Triage TOX Drug Screen was 92.4–100% compared with UPLC-TMS; however, the Triage TOX Drug Screen results showed some discordant cases including acetaminophen, amphetamine, benzodiazepine, opiates, and tricyclic antidepressants. The overall performance of the Triage TOX Drug Screen assay was comparable to that of UPLC-TMS for screening of drug intoxication in hospitals. This assay could constitute a useful screening method for drugs of abuse and therapeutic drugs in urine.
Acetaminophen ; Amphetamine ; Antidepressive Agents, Tricyclic ; Benzodiazepines ; Chromatography, Liquid ; Immunoassay ; Mass Screening ; Methods ; Street Drugs* ; Tandem Mass Spectrometry ; Toxicology ; Triage*

OBJECTIVES: The aim of this study was to investigate the clinical and demographic characteristics and some laboratory findings of hospitalized patients with acute opioid toxicity and rhabdomyolysis. METHODS: This cross-sectional study investigated 354 patients hospitalized at Baharloo Hospital in Tehran in 2014 with acute illicit drug toxicity. Data were collected using an investigator-made checklist. The collected data (such as mortality rate, demographic data, and renal function tests, as well as serum biochemical findings) were analyzed by descriptive statistics and the chi-square test. RESULTS: A total of 354 patients were admitted to the hospital in 2014 with acute illicit drug toxicity, including 291 males and 63 females. The total number of patients with rhabdomyolysis was 76 (21.5% of the total), of whom 69 (90.8%) were male and 7 (9.2%) were female. Most cases of rhabdomyolysis were associated with methadone abuse, followed by opium abuse. Rhabdomyolysis was most common in those 20–29 and 30–39 years old, with methadone and opium the most commonly abused illicit drugs. The mean blood urea level was 3.8±1.0 mg/dL, and the mean serum potassium and sodium levels were 3.8±0.3 mg/dL and 140.4±4.0 mg/dL, respectively. Five patients, all of whom were male, passed away due to severe renal failure (6.5%). CONCLUSIONS: Toxicity caused by opioids is associated with clinical complications and laboratory disorders, such as electrolyte disorders, which can lead to lethal or life-threatening results in some cases. Abnormal laboratory test findings should be identified in patients with opioid toxicity in order to initiate efficient treatment.
Analgesics, Opioid ; Checklist ; Critical Care* ; Cross-Sectional Studies ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Intensive Care Units* ; Iran* ; Male ; Methadone ; Mortality ; Opium ; Poisoning* ; Potassium ; Renal Insufficiency ; Rhabdomyolysis* ; Sodium ; Street Drugs ; Urea

OBJECTIVES: The aim of this study was to investigate the clinical and demographic characteristics and some laboratory findings of hospitalized patients with acute opioid toxicity and rhabdomyolysis.METHODS: This cross-sectional study investigated 354 patients hospitalized at Baharloo Hospital in Tehran in 2014 with acute illicit drug toxicity. Data were collected using an investigator-made checklist. The collected data (such as mortality rate, demographic data, and renal function tests, as well as serum biochemical findings) were analyzed by descriptive statistics and the chi-square test.RESULTS: A total of 354 patients were admitted to the hospital in 2014 with acute illicit drug toxicity, including 291 males and 63 females. The total number of patients with rhabdomyolysis was 76 (21.5% of the total), of whom 69 (90.8%) were male and 7 (9.2%) were female. Most cases of rhabdomyolysis were associated with methadone abuse, followed by opium abuse. Rhabdomyolysis was most common in those 20–29 and 30–39 years old, with methadone and opium the most commonly abused illicit drugs. The mean blood urea level was 3.8±1.0 mg/dL, and the mean serum potassium and sodium levels were 3.8±0.3 mg/dL and 140.4±4.0 mg/dL, respectively. Five patients, all of whom were male, passed away due to severe renal failure (6.5%).CONCLUSIONS: Toxicity caused by opioids is associated with clinical complications and laboratory disorders, such as electrolyte disorders, which can lead to lethal or life-threatening results in some cases. Abnormal laboratory test findings should be identified in patients with opioid toxicity in order to initiate efficient treatment.
Analgesics, Opioid ; Checklist ; Critical Care ; Cross-Sectional Studies ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Intensive Care Units ; Iran ; Male ; Methadone ; Mortality ; Opium ; Poisoning ; Potassium ; Renal Insufficiency ; Rhabdomyolysis ; Sodium ; Street Drugs ; Urea

Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEP(C230X−/−) mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEP(C230X−/−) mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine.
Analgesia* ; Animals ; Brain ; Codon, Nonsense ; Dopamine ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; Ethylnitrosourea ; Fertilization in Vitro ; Gene Library ; Mass Screening ; Mice ; Morphine* ; Phosphotransferases ; Protein Tyrosine Phosphatases ; Receptors, Opioid ; Reward* ; Street Drugs ; Substance Withdrawal Syndrome*

As an annual function of the Therapeutic Drug Monitoring Subcommittee of Korean Association of External Quality Assessment Service (K-EQAS), we organised two trials for an external quality assessment of therapeutic drug monitoring (TDM) and testing for drugs of abuse (DOA) in 2015. For the TDM assessment, we sent low- and high-level control materials from various clinical institutions, and for the DOA testing, we sent positive and negative control materials. The number of participating laboratories was 105 for the TDM trial and 106 for the DOA test. The average number of drug items provided was 5.6 per institution. The most commonly tested substances, in descending order, were: valproic acid, digoxin, vancomycin, tacrolimus, and carbamazepine. The mean inter-laboratory coefficients of variation for low- and high-level TDM control materials were 7.3% and 7.4%, respectively. The most widely used TDM analysers were the Architect i System (Abbott Diagnostics, USA), followed by the Cobas Integra (Roche Diagnostics, Switzerland) and the Cobas c501 analyser (Roche Diagnostics). The number of participating laboratories for the DOA analysis was 16% higher that than of our 2014 study. In 98.6% of cases, our analysis confirmed the reliabilityviability of the tests at participating DOA laboratories in both trials. In the external quality assessment of TDM by the TDM subcommittee of K-EQAS in 2015, the overall performance of TDM testing was found to be similar to that reported in previous years, and inter-laboratory precision was higher than that of 2014. Continuous improvement in the quality of TDM testing through participation in a proficiency-testing program will remain necessary in the future.
Carbamazepine ; Digoxin ; Drug Monitoring* ; Korea* ; Laboratory Proficiency Testing ; Street Drugs* ; Tacrolimus ; Valproic Acid ; Vancomycin